Biophysical constraints on mRNA decay rates shape macroevolutionary divergence in steady-state abundances

Area of Science:

• Evolutionary biology
• Genomics
• Molecular biology

Background:

• Gene expression evolution drives phenotypic divergence.
• Previous studies used bulk RNA data, limiting insights into cellular processes.
• Steady-state mRNA levels suggest evolutionary constraints.

Purpose of the Study:

• Investigate cellular processes underlying species-specific gene expression divergence.
• Develop a novel method using single-cell data and biophysical models.
• Identify key molecular mechanisms driving evolutionary changes in gene expression.

Main Methods:

• Utilized multi-species single-cell RNA sequencing data.
• Applied biophysical models to estimate mRNA transcriptional bursting, splicing, and decay rates.
• Developed and fitted phylogenetic models to comparative data.

Main Results:

• Estimated species-specific mRNA transcriptional burst, splicing, and decay rates.
• Identified biophysical constraints on mRNA decay rates.
• Found that variation in transcriptional bursting primarily drives macroevolutionary expression divergence.

Conclusions:

• Macroevolutionary divergence in gene expression is significantly influenced by transcriptional bursting.
• Biophysical constraints on mRNA decay play a role but are secondary to bursting.
• This study provides a new framework for analyzing evolutionary changes at the molecular level.